Exotic species have demonstrated their utility as models for the study of a wide range of hereditary and infectious diseases and physical traits. However, to fully interpret the results of these studies, it is necessary to understand their evolutionary history. This involves not only a more precise description of the phylogenetic relationships among species, but also an assessment of the uniqueness among wild populations and knowledge of historic patterns of gene flow. Our primary animal model has been the domestic cat and their exotic relatives and wild populations. As a crucial step in this process, we have developed the foremost collection of biological samples from captive and wild populations of cats, which has provided the theoretical and conceptual framework for our research. The recently-released whole genome sequence of the domestic cat has provided an important tool for our research and is greatly accelerating the pace of gene discovery and comparative genomic inference. Among the cat species, we have recently focused efforts on Asian species, including the tiger, leopard, clouded leopard, leopard cat, and fishing cat, as well as Canada lynx, bobcat, and puma. Many of these studies integrate and focus on host/virus interactions, such as with FeLV and FIV in Florida Panthers and FIV and CDV in African lions. Our comparative genomic studies have expanded to include the alpaca and the pangolin. We will complete development of a radiation hybrid (RH) map of the alpaca in 2006 which will facilitate the study of candidate genes for inherited diseases in camelids and related ungulate species, including several related to human disorders. Study of the pangolin, a group of species distributed in Africa and Asia and the closest relatives to carnivores, will provide good models for comparative genomic studies among these increasingly well-studied groups. Our research on camelids and pangolins will be increasingly important given the inclusion of both the alpaca and the pangolin on the short list of species for low-coverage, whole-genome-sequencing.